TY - JOUR
T1 - Novel biomarkers in bone pathophysiology
T2 - Establishing reference intervals and biological variations estimates for serum leptin, sclerostin, lipocalin-2, osteoprotegerin, resistin and Dickkopf-related protein-1 from the European biological variation study (EuBIVAS) populations
AU - Sansoni, Veronica
AU - Lombardi, Giovanni
AU - Díaz–Garzón, Jorge
AU - Calle, Pilar Fernández
AU - Bartlett, William A.
AU - Coşkun, Abdurrahman
AU - Itkonen, Outi
AU - Jonker, Niels
AU - Sandberg, Sverre
AU - Aarsand, Aasne K.
AU - Banfi, Giuseppe
AU - Carobene, Anna
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/3/15
Y1 - 2025/3/15
N2 - A range of biomarkers of bone metabolism are thought to mediate adipose tissue-bone crosstalk and fulfil a homeostatic role. While considered clinically relevant, their utility and application appears limited by lack of data characterising biological variability and reference intervals rather than by analytical issues. We have therefore studied the biological variation (BV) of these biomarkers. Concentrations of Dikkopf-related protein 1, leptin, osteoprotegerin, sclerostin, lipocalin2 (Lcn2) and resistin were measured by Luminex assays in serum samples from the EuBIVAS study. Samples were taken once per week, over 10 consecutive weeks, from 91 subjects in cohorts from 5 European countries. Estimates of analytical variation (CVA), within-subject (CVI) and between-subject (CVG) BV were calculated and analytical imprecision (CVAPS) and analytical bias (BAPS) specifications, index of individuality (II), reference change values (RCV) for increase and decrease and the number of samples required to estimate the homeostatic set points (NHSPs) were derived. Mean concentrations differed between males and females for leptin, osteoprotegerin, and sclerostin, and for osteoprotegerin and sclerostin between females in fertile and menopausal ages. No male-to-female differences were observed in CVI estimates. Index of individuality was below 0.6, for all measurands. Determination of reference intervals (RI) limits indicated that all, with the exception Lcn2, described data which were non-gaussian distributed and that only leptin differed between sexes. Availability of high-quality biological variation enables objective assessment of the bone metabolism biomarker results which may enhance their clinical utility. The data indicates that they exhibit significant individuality.
AB - A range of biomarkers of bone metabolism are thought to mediate adipose tissue-bone crosstalk and fulfil a homeostatic role. While considered clinically relevant, their utility and application appears limited by lack of data characterising biological variability and reference intervals rather than by analytical issues. We have therefore studied the biological variation (BV) of these biomarkers. Concentrations of Dikkopf-related protein 1, leptin, osteoprotegerin, sclerostin, lipocalin2 (Lcn2) and resistin were measured by Luminex assays in serum samples from the EuBIVAS study. Samples were taken once per week, over 10 consecutive weeks, from 91 subjects in cohorts from 5 European countries. Estimates of analytical variation (CVA), within-subject (CVI) and between-subject (CVG) BV were calculated and analytical imprecision (CVAPS) and analytical bias (BAPS) specifications, index of individuality (II), reference change values (RCV) for increase and decrease and the number of samples required to estimate the homeostatic set points (NHSPs) were derived. Mean concentrations differed between males and females for leptin, osteoprotegerin, and sclerostin, and for osteoprotegerin and sclerostin between females in fertile and menopausal ages. No male-to-female differences were observed in CVI estimates. Index of individuality was below 0.6, for all measurands. Determination of reference intervals (RI) limits indicated that all, with the exception Lcn2, described data which were non-gaussian distributed and that only leptin differed between sexes. Availability of high-quality biological variation enables objective assessment of the bone metabolism biomarker results which may enhance their clinical utility. The data indicates that they exhibit significant individuality.
KW - Bone-adipose tissue crosstalk
KW - Clinical implementation
KW - EuBIVAS
KW - Metabolic inflammation
UR - http://www.scopus.com/inward/record.url?scp=85219145019&partnerID=8YFLogxK
U2 - 10.1016/j.cca.2025.120213
DO - 10.1016/j.cca.2025.120213
M3 - Article
C2 - 40010661
AN - SCOPUS:85219145019
SN - 0009-8981
VL - 570
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
M1 - 120213
ER -